Prolonged exposure to loud noise causes hair cell damage, more readily to outer hair cells, and is a common pathological feature of noise-induced hearing loss. Much remains to be discovered about the cellular mechanisms that occur within the inner ear following exposure to loud, damaging auditory stimuli (noxious noise). The inner ear contains two types of neurons, type I afferents that make synaptic connections with inner hair cells and type II afferents that innervate outer hair cells. It is well known that type I affeents transmit auditory information following stimulation of inner hair cells; however, the biological roe of type II afferents remains unknown. Type II afferents share anatomical similarities with somatosensory nociceptors that detect damaging stimuli throughout the body. Based on their anatomical morphology and location (beneath outer hair cells), we hypothesize that type II neurons act as nociceptors within the cochlea that detect and/or respond to noxious noise. These results may show for the first time, the physiological role type II afferents may have. Using two animal models that have silenced type I afferents: (1) ouabain treated mice and (2) VGLUT3 KO mice, the proposal aims to determine the physiological activators of type II afferents. We have developed two assays that use noxious noise stimulation to specifically test if noxious noise activates type II afferents. Our preliminary results show neuronal activation and behavioral responses to noxious noise in wild type animals validating our experimental approaches. This proposal aims to clarify the cellular mechanisms that occur within the inner ear following exposure to noxious noise, and ultimately test for the existence of nociceptor neurons in the cochlea. The information that is obtained will advance understanding of type II afferent connectivity and function, and will help clarify how noxious noise is detected. PUBLIC HEALTH RELEVANCE: With more than 5 million children estimated to suffer from noise induced hearing loss, much remains to be discovered about the cellular mechanisms that occur within the inner ear following exposure to loud, damaging auditory stimuli. Here we will address whether a special type of neuron, type II afferents, located in the inner ear play an important role in detecting and/or responding to damaging noises.